Pyrimidyl cyanoalkyl sulphides



Patented Sept. 15, 1942 2,295,559 PXBJIVHDYL CYANOALKYL SULPHIDES Gaetano F. DAlelio and James W. Underwood, Pittsfield, Mass, assignors to General Electric Company, a corporation of New York no Drawing. Application May 27, 1941,

Serial No. 395,425 11 Claims. (01. 260-251) This invention relates to new chemical compounds and more particularly to pyrimidine derivatives. The invention especially is concerned with the production of new and useful pyrimidyl cyanoalkyl sulphides.

The pyrimirbl cyanoalkyl sulphides of this invention may be illustrated graphically by the following general formula:

In the above formula 11. represents an integer and is at least 1 and not more than 3, a: is an integer and is at least 1 and not more than 2, and R. represents a member of the class consisting of hydrogen and monovalent hydrocarbon and halohydrocarbon radicals, numerous examples of which hereafter are given. Since n: represents an integer which is l or 2, it will be seen that the linkage of the cyanoalkyl group to the-sulphur atom in all cases will be alpha or beta to the cyano group. 'It also will be observed that linkage of the pyrimidyl grouping to the sulphur atom is through a carbon atom. From a consideration of the formula it further will be seen that when n is 3 there will be no amino groups attached to the pyrimidyl nucleus. I

Illustrative examples of monovalent hydrocarbon radicals which R in the above formula may be are alkyl (e, g., methyl, ethyl, propyl, isopropyl, butyl, secondary butyl, isobutyl, amyl, isoamyl, hexyl, etc.) including cycloaliphatic (e. g., cyclopentyl, cyclopentenyl, cyclohexyl, 'cyclohexenyl, cycloheptyl, etc); aryl (e. g, phenyl, di-

'phenyl, naphthyl, etc.) alkaryl (e. g., tolyl, xylyl,

ethylphenyl, propylphenyl,isopropylphenyl, etc.) aralkyl (e. g., benzyl, phenylethyl, phenylpropyl, etc); and their homologues, as well as those groups with one or more of their hydrogen atoms substituted by, for example, a halogen. Specific examples of halogeno-substituted hydrocarbon radicals are chlormethyl, chlorcyclohexyl, chlorphenyl, dichlorphenyl, ethyl chlorphenyl, phenyl chlorethyl, bromethyl, bromtolyl, etc. Preferably.

R is hydrogen.

Our new pyrimidyl cyanoalkyl sulphides may be used as chemotherapeutic agents and, also, as intermediates in the preparation of other compounds. For example, they may be employed as intermediates in the preparation of derivatives thereof such as imido ether, amidine, acyl, ureido, hydrazino, etc., derivatives of the individual pyrimidyl cyanoalkyl sulphide. These new organic sulphides are especially valuable as re actants in the preparation of synthetic resinous compositions. Thus, they may be condensed with, for instance, aldehydes, including polymeric aldehydes and aldehyde-addition products, to yield condensation products of particular utility in the plastics and coating arts. Such condensation products are more fully described and claimed in our copending application Serial No. 395,424, filed concurrently herewith and assigned to the same assignee as the present invention. In our copending application Serial No. 441,862, filed May 5, 1942, which application is a continuation-in-part of the present application and of application Serial No. 395,424, we have more fully described and have specifically claimed' compositions of matter comprising the product of reaction of ingredients comprising an aldehyde and a compound corresponding to the general formula where n represents an integer and is at least 1 Various methods may be employed to produce the chemical compounds of this invention. We prefer to prepare them by effecting reaction between 3. mercapto pyrimidine and a mono-halogenated alkyl nitrile in the presence of a hydro- Illustrative examples of merhalide acceptor. capto pyrimidines which may be used, depending upon the particular pyrimidyl cyanoalkyl sulphide desired, are:

4,6-diamino Z-mercapto pyrimidine 2,6-diamino 5ethyl 4-mercapto pyrimidine 6-amino 2,4-dimercapto pyrimidine 2-amino 5-benzyl, 4,6-dimercapto pyrimidine 5-methyl 2,4,6-trimercapto pyrimidine 2,4,6-trimercapto pyrimidine 4,6-di-(methylamin'o) Z-mercapto pyrimidine 4,6-dianilino Z-mercaptopyrimidine ,2,6-di(cyclohexylamino) 4-mercapto,pyrimidine 4,6-ditoluido 5-phenyl 2-mercapto pyrimidine 4-benzylamino G-methylamino 2-mercapto pyrimidine, which also may be named 4-methyl= amino 6-benzylamino Z-mercapto pyrimidine Typical examples of mono-halogenated alkyl nitriles which may be employed, depending upon the particular end-product sought," are Chloracetonitrile Alpha-chlorpropionitrile Beta-brompropionitrile Beta-chlorbutyronitrile Phenyl chloracetonitrile Beta-bromo gamma-cyclohexyl butyronitrile Beta-chloro alpha-ethyl propionitriie Alpha-bromo alpha-methyl beta-chlorphenyl butyronitrile 'monium*bases (e. g., tetramethyl ammonium hydroxide, etc.), and the like. Preferably the hydrohalide acceptor is one that will react with the mercapto pyrimidine to form a water-soluble salt. Examples of such preferred acceptors'are sodium and potassium hydroxides.

The reaction between the mercato pyrimidine and the mono-halogenated alkyl nitrile may be carried out in any suitable manner, but preferably is effected in the presence of a suitable solvent or mixtureof solvents. Although various solvents or solvent mixtures may be employed we prefer, for economic reasons and because of their eminent suitability, to use water or a mixture of water and alcohol. The reaction may be carriedout under a variety of temperature and pressure conditions, for instance at normal or at elevated temperatures and at atmospheric, sub-atmospheric or super-atmospheric pressures.

. The above reaction may be represented by thefollowing general equation:

n(hydrohalide acceptor) In the above equation X represents halogen and R, n and a: have the same meanings as given above with reference to the general Formula I for the pyrimidyl cyanoalkyl sulphides of this invention.

The chemical compounds of this invention also may be prepared by effecting reaction between a halo-pyrimidine and a mono-mercapto alkyl nitrile in the presence of a hydrohalide acceptor. This reaction may be carried out by any suitable means but preferably is effected in the presence of an anhydrous solvent, e. g., alcohol. The other conditions of reaction may be the same as described above with reference to the first-mentioned method of preparation.

Illustrative examples of halogenated pyrimidines which may be used, depending upon the desired end-product, are:

'6-chloro 2,4-diamino pyrimidine 6-iodo 2,4-diamino pyrimidine 4,6-dichloro 2-amino pyrimidine 4,6 -jdichloro 5-methyl '2-amino pyrimidine 2,4,6-trichloro pyrimidine 6-chloro 2,4-di-(methylamino) pyrimidine 4,-chloro 2-amino 6-anilino pyrimidine 2 -ch1oro 'i-toluido fi-ethylamino pyrimidine 4,6-dibromo 2-cyclohexylamino 5-phenyl pyrimi'- dine dine Illustrative exainples of mono-mercapto alkyl nitriles which may be used, depending upon the particular pyrimidyl cyanoalkyl sulphide desired, are:

tyronitrile Alpha-mercapto beta-tolyl butyrcnitrile The hydrohalide acceptor may be the'sa'me as described above with reference tothe first-named method of preparing the compounds of this invention.

The general reaction for this alternativemethod of preparing our new chemical compounds is illustrated by the following equation:

lo ydmhllide t t Y 60 In this equation R, x, n and a: have the same meanings as defined hereinbeforewith reference to Formula I and Equation 11. r

A more specific illustration of how these new compounds may be prepared is described below with reference to the preparation of 4,6-diamino pyrimidyl-2 cyanomethyl sulphide, the formula for whichis. a

iv .HC \N HzN- /JJS-ICH:CN

N/ All parts are by weight.

' Example 4 Parts 4,6-diamino 2-mercapto' pyrimidine 158 Chloracetonitrile (mono-chloracetonitrile 84 Sodium hydroxide (hydrohalide acceptor)-.. 44

The diamino mercapto pyrimidine and the sodium hydroxide were dissolved in a solvent comprising 2,000 partswater and 2,000 parts alcohol. The chloracetonitrile was added to the resulting 6'-iodo 2,4-di-(benzylamino) 5-benzyl pyrimi Beta-mercapto alpha-benzyl. alpha-methyl bu-' cyanoethyl) sulphide] 7 2,295,559 solution. The mixture was stirred at room tem-'" perature for 24 hours. By this time a precipitate x of the product (4,6-diamino pyrimidyl-2 cyanomethyl sulphide) had formed. In order to in- I {I I sure a complete reaction the mix was heated for 5 F one hour on a boiling water bath. The mixture 5 was cooled. The product was filtered OE and th mu m washed well with hot water. A yield of 159 parts m (mums y D of 4,6-diamino pyrimidyl-2 cyanomethyl sulphide r was obtained. More could be recovered from the '10 xi mother liquor by evaporation.

As will be readily understood by those skilled g a in the art; when it is desired to produce com- Q E pounds containing a single monoamino pyrimidyl grouping and two cyanoalkyl sulphide groupings 6 amm pyflmmfiu d1 (mom-M171 sulphide) or compounds containing a pyrimidyl grouping v l4-amino pyrlmidyl-2,6 dl-(cyanomethyl sul hide)! and three cyanoalkyl sulphide groupings, then n the starting reactants and proportions of reac- (5N tants are chosen so as to yield the desired prodx11 ucts in accordancewith methods such as above H: .given by way of illustration. CHPC From the foregoing description it will be seen .ll that the present invention provides new and NC CH CH S Q useful pyrimidyl cyanoalkyl sulphides, examples C h H: Hr. of which are pyrimidyl tri-(cyanomethyl sulphide), pyrimidyl tri-(cyanoethyl sulphide), the r -umgg f g phs-phen p pyl)' monoamino pyrimidyl di-(cyanomethyl' su1-' p phides), the monoamino pyrimidyl di-(cyano- NH, ethylsulphides), the diamino pyrimidyl monox (cyanomethyl sulphides) and the diamino 4 pyrimidyl mono-(cyanoethyl sulphides). Other e and more specific examples of these new com pounds are shown below: i Nil-CH8 B-amino pYrimidyH-cyanomethyM-betacyanoethyldisulphlde I Nn-cm v I Cs k- N 02135 cm-nn-c -s-cH-cH-cN xw v a N 40 Cfir-HN-P) c s-cmcu 4,6-dl-(methylamlno) 5-phenyl pyrimidyl-2 bets-(alpha-phenyl 'p cyanobutyl) sulphide V NH C 4-anilino B-methyiamino pyrlmidyl-2 cynnomethyl sulphide 6H6 11H: VI

' H(3/ \N C rCt u XV CH -HN( J (2SJJHCH:CN E 1 ILN- CSCHzGHa-GN N n l 4,8-dlanilino pyrimidyl-ZbetaKgarnma-cyclohexyl oyanopropyl) sulphlde y 1 4,6-diamino pyrlmidyl-Z beta-cyanoethylsnlphide NH: N'H, vn

0132-? \N xvr cHr-cH-s-c )J-Nn, i l, V N N N 2, a an mi-48111 thlsulhid [2m sgngu S$mw ufinififlirfifi smgmdil pyl'lmidyl'z alPhBflanoethYl sulphide What we claim as new anddeside to secure by w Letters Patent of the United States is:

n CH: 1. compounds corresponding to the 'nc-bm-cn-s-o -s-oH-cH=-oN mm Y m N 'i [6-toluido 5-ethylpyrimldyl-2,4dl-(beta-cyanopropylsulphide)! \N I -(RHN),:[ -{S(GR1)-CN] H01 7 1x 6 A \N s F I I where n is an integer and is at least 1 and not NC CH"CH S C NH CH more than 3, a: is an integer and is at least 1 and H401 N not more than 2, and B. is a member of the class consisting of hydrogen and monovalent hydrocarbon and halo-hydrocarbon radicals.

2. Chemical'compounds as in claim 1 wherein R represents hydrogen. p a

3. Chemical compounds as in claim 1 wherein R represents hydrogen and a: is 1.

4. Pyrimldyl-2,4,6 tri-(cyanomethyl sulphide).

5. A monoamino pyrimidyl di-(cyanomethyl sulphide).

6. 6-aminopyrimidy1,-2,4 di-(cyanomethyl suI- phide).

"l. A di mino pyrimidyl cyanomethyl sulphide. ,8. 4,6-d o pyrimidy1-2 cyanomethyl sulphide.

9. The method of preparing chemical compounds corresponding to the general formula (I) i RC N 1 4mm) --{s-(cR, .-'c1-r] where n is an integer and is atleast 1 and not morethan 3, :c is an integer and is at least 1 and not more than 2, and R is a member of the class consisting of hydrogen and monovalent hydrocarbon and halo-hydrocarbon radicals, said method comprising eiiecting reaction, in the presence of a hydrohalide acceptor, between (1) a mercapto pyrimidine corresponding to the general formula.

m R-C N l- 4] Tsn),

where 'n and R have the meanings above given, and (2) mono-halogenated alkyl nitrile corresponding to the general formula GAE'I'ANOF. D'ALELIO. JAMES W. UNDI 'QRWOOD. 

